Integrated understanding of taste receptor-mediated intestinal homeostasis mechanisms

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Osaka Metropolitan University (2022-2023); Osaka City University (2021)
• Principal Investigator: Fujiwara Yasuhiro 大阪公立大学, 大学院医学研究科, 教授 (40285292)
• Co-Investigator(Kenkyū-buntansha): 古株 彰一郎 九州歯科大学, 歯学部, 教授 (30448899) ; 細見 周平 大阪公立大学, 大学院医学研究科, 講師 (60554938)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 味覚受容体 / 脂肪肝炎モデル / 薬剤性腸炎モデル

Outline of Final Research Achievements

Intestinal epithelium-specific Tas1r3 knockout mice (Tas1r3ΔIEC) and control mice (WT) were fed a high-fat, high-cholesterol diet (HFCD) for 8 weeks to evaluate liver disease. The Tas1r3ΔIEC HFCD group showed lower lipid droplet deposition and triglyceride (TG) content than the WT HFCD group, as well as lower expression levels of CYP2E1 and Alox15 mRNA. Additionally, in the colitis model, there was no difference in DSS-induced colitis, but in the indomethacin-induced enteritis model, the Tas1r3ΔIEC group showed milder histological inflammation and lower expression of inflammatory cytokines compared to the WT group. These results suggest that taste receptors may be a potential new therapeutic target for metabolic diseases and enteritis.

Free Research Field

味覚受容体

Academic Significance and Societal Importance of the Research Achievements

腸管上皮特異的な味覚受容体（Tas1r3）欠損マウスを用いた基礎的研究により、味覚受容体の代謝異常関連疾患における役割の理解や、また、薬剤誘発腸炎マウスモデルにおける味覚受容体の役割についても新規知見が得られた。糖質や各種アミノ酸の味覚受容体を介した代謝異常関連疾患や炎症性腸疾患への新規治療薬の探索につながる研究成果を得られた。また、人工甘味料の肝疾患・腸疾患への影響の理解にもつながる結果であった。